Our studies of various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment comprise three areas: (1) coronavirus infection in ocular and optic nerve cells; (2) the possible roles of viruses in human diseases; and (3) antiviral therapeutic actions of cytokines and drugs. A fourth area of study initiated during the past year is the evaluation of molecular diagnosis and pathogenesis of cytomegalovirus infections in man. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Initial retinal damage is followed by clearance of the virus and progressive retinal degeneration, even months after the virus is gone. In vitro studies and electron microscopic evaluation of in situ infection indicate that the virus replicates predominantly in Muller cells and can also be detected in retinal pigment epithelium (RPE) and photoreceptor cells. These results demonstrate that the virus can induce biochemical and morphological changes in the retina that persist and progress long after the virus is detectable. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. The need for effective drug treatment and prevention of herpes virus and other viral diseases has assumed growing importance. We found that leukoregulin, a naturally occurring immunologic cytokine, not only increases the antiviral actions of the drug acyclovir but also directly inhibits herpes simplex virus replication. These findings, which demonstrate that combination immunotherapy and chemotherapy can produce substantial inhibition of herpes virus replication, provide a rationale for the application of this approach to the treatment of virus infections.